本論文描述了一項檢測技術用以分析磁性樣品特性，本研究開發微型交流磁導儀磁結合了磁粒子頻譜分析系統（Magnetic Particle Spectrum Analyzer, MPS），可測定磁性粒子的磁化頻譜，預測合成磁性粒子於醫學造影中的適用性[1]，並成功開發以5th harmonic分析磁性樣品量測技術。
在系統性能提升部分，優化了線圈架構提升磁場產生振幅達約354.57 Oe。具有足夠強度的激發磁場驅動致磁性粒子非線性響應產生諧波信號，大幅提升訊雜比（Signal-to-noise ratio, SNR），實現了對微量磁性樣品的高靈敏度檢測。並擴大檢測功能性磁珠的直徑範圍，從原本的奈米擴大至微米等級，增加功能性磁珠應用價值。
為了驗證磁粒子頻譜分析系統發展生物醫學可行性，我們將之應用於磁性生物標記免疫檢測，檢測CRP抗原。透過標靶磁性粒子與生物抗原結合，量測磁性叢集所致粒徑變化對應磁化強度的改變，可辨別出1 ppm抗原濃度，符合目前心肌梗塞及中風風險評估之標準，允許在生物研究中進行更精確的模擬。此技術提供快速經濟方法來表徵磁特性，並且適用於多種檢測類型。

This paper describes a detection technique for analyzing the characteristics of magnetic specimen. We developed a Miniature AC Susceptometer that combines the Magnetic Particle Spectrum Analyzer (MPS) to measure the magnetization spectrum of magnetic particles and predict synthetic magnetic particle properties. The applicability of particles in Magnetic Particles Imaging [1], and finally, we successful developed magnetic specimen measurement technique with 5th harmonic analysis.
Regarding to the system performance improvement, the excitation coil structure is optimized to increase the magnetic field to 354.57 Oe approximately. The high strength excitation magnetic field drives the nonlinear response of the magnetic particles to generate harmonic signals, which boosted signal-to-noise ratio significantly, extending the detecting range of diameter of functionalized magnetic particles from the nanometers (nm) to Microns (µ), and increasing the application of functionalized magnetic particles.
In order to verify the biomedical feasibility of the magnetic particle spectrum analyzer, we tried to apply it to the magnetic labeled immunoassay, detecting the CRP antigen. Measuring the behavior of magnetization increments in magnetic specimen by conjugating the biofunctionalized magnetic nanoparticles (BMNs) with biotargets in liquid magnetic immunoassays, the antigen of 1 ppm concentration can be discriminated, which complies with the current risk assessment criteria for myocardial infarction and stroke, achieving more accurate simulation in biological research.
 
Therefore, a high sensitive detection of magnetic particles can be achieved. The detection limit of iron content was identified. The Miniature AC Susceptometer shows the feasibility for biomedical application after combination with the microfluidics devices.

[1] S. Biederer, T. Knopp, T. Sattel, K. Lüdtke-Buzug, B. Gleich, J. Weizenecker, J. Borgert, and T. Buzug, “Magnetization response spectroscopy of superparamagnetic nanoparticles for magnetic particle imaging,” J. Phys. D: Appl. Phys., vol. 42, p. 205007, 2009.
[2] Gleich B, and Weizenecker J, “Tomographic imaging using the nonlinear response of magnetic particles,” Nature, vol. 435, no. 7046, 1412-7, Jun 2005.
[3] Weizenecker J, Borgert J, and Gleich B. “A simulation study on the resolution and sensitivity of magnetic particle imaging,” Phys. Med. Biol, vol. 52, no. 21, p. 6363-74, Nov 2007.
[4] Liang ZP, and Lauterbur PC: Principles of Magnetic Resonance Imaging, New York: IEEE, Inc.; 2000.
[5] Rudolf Hergt, Silvio Dutz, Robert Müller, and Matthias Zeisberger. “Magnetic particle hyperthermia: nanoparticle magnetism and materials development for cancer therapy,” Journal of Physics: Condensed Matter, vol. 18, no. 38, Sep 2006
[6] Hergt R, Dutz S, and Röder M., “Effects of size distribution on hysteresis losses of magnetic nanoparticles for hyperthermia,” Journal of Physics Condensed Matter, vol. 20, no. 38, p. 385214, Sep. 2008.
[7] Paul M. Ridker, M.D., Charles H. Hennekens, M.D., Julie E. Buring, Sc.D., and Nader Rifai, “C-Reactive Protein and Other Markers of Inflammation in the Prediction of Cardiovascular Disease in Women” The New England Journal of Medicine, ORIGINAL ARTICLE, Mar 2000.
[8] 黃鈺菁。《C-反應蛋白(CRP)與高敏感性C-反應蛋白(hs-CRP)在心血管疾病中扮演的角色 》秀傳醫療社團法人秀傳紀念醫院檢驗科，檢自https://www.scmh.org.tw/dept/lab/show/Preview/c------crp------c------hs-crp-----------------.html
[9] Pierre-Michel Déjardin, and Yuri P. Kalmykov, “Relaxation of the magnetization in uniaxial single-domain ferromagnetic particles driven by a strong ac magnetic field” Journal of Applied Physic , 2009.
[10] Chen K-L, Chen J-H, Liao S-H, Chieh J-J,Horng H-E, Wang L-M, et al., “Magnetic clustering effect during the association of biofunctionalized magnetic nanoparticles with biomarkers,” PLoS ONE, vol. 10, no.8, p. e0135290, 2015.
[11] Fredrik Ahrentorpa et al., “Sensitive High Frequency AC Susceptometry in Magnetic Nanoparticle Applications” AIP Conference Proceedings, vol. 1311, no. 213, 2010.
[12] P Laurent, J F Fagnard, B Vanderheyden, N Hari Babu, D A Cardwell, M Ausloos, and P Vanderbemden. “An AC susceptometer for the characterization of large, bulk superconducting samples” Measurement Science and Technology, vol. 19, no. 8, Jul 2008
[13] 黃念祖。《應用於血液檢測之生醫微流道晶片》 臺大電機系科普系列，What's fun in EE，檢自http://ee.ntu.edu.tw/upload/hischool/doc/2013.11.pdf
[14] Yung-Sheng Lin, Ming-Yuan-Lee, Chih-Hui Yang, and Keng-Shiang Huang, “Biomedical Devices for Pathogen Detection Using Microfluidic Chips” Current Proteomics, vol. 11, no. 2, pp. 116-120, 2014
[15] Weaver J B, Rauwerdink A M, Sullivan C R, and Baker I, “Frequency distribution of the nanoparticle magnetization in the presence of a static as well as a harmonic magnetic field.” Med. Phys, vol. 35, no. 3, p. 1988–94, May 2008.
[16] Stefaan Vandendriessche, Ward Brullot, Dimitar Slavov, Ventsislav K. Valev, and Thierry Verbiest, “Magneto-optical harmonic susceptometry of superparamagnetic materials.” Appl. Phys. Applied Physics Letters, vol. 102, no. 16, Mar 2013
[17] Knobel M1, Nunes WC, Socolovsky LM, De Biasi E, Vargas JM, and Denardin JC, “Superparamagnetism and other magnetic features in granular materials: a review on ideal and real systems.” J. Nanosci. Nanotechnol, vol. 8, no. 6, Jun 2008.
[18] Kai Wu, Akash Batra, Shray Jain, and Jian-Ping Wang, “Magnetization Response Spectroscopy of Superparamagnetic Nanoparticles Under Mixing Frequency Fields.” IEEE TRANSACTIONS ON MAGNETICS, vol. 52, no. 7, Jul 2016.
[19] 杜怡君、張毓娟、翁乙壬、蘇怡帆、陳世毓、梁哲銘、葉巧雯、吳信璋、卓育泯。《磁性基本特性及磁性材料應用》國立台灣大學化學系，檢自https://www.ch.ntu.edu.tw/~rsliu/teaching/pdf97/material/5.pdf
[20] NEIL SMITH, “Reciprocity Principles for Magnetic Recording Theory.” IEEE TRANSACTIONS ON MAGNETICS, vol. MAG-23, no. 4, Jul 1987.
[21] Shu-Hsien Liao, and Yu-Kai Su. “Determining the time-dependent effective relaxation time ofbiofunctionalized magnetic nanoparticles conjugated with biotargetsby using a high-TcSQUID-based ac susceptometer for a magneticimmunoassay.” Sensors & Actuators: B. Chemical. vol. 238, pp. 66-70, 2017.
[22]Yulin Yuana, Shanshan Lib, Yewei Xueb, Jintao Liangb, Lijie Cuib, Qingbo Lib,Sufang Zhouc, Yong Huangb,c, Guiyin Lib,c, and Yongxiang Zhao, “A Fe3O4@Au-basedpseudo-homogeneous electrochemical immunosensor for AFP measurement using AFP antibody-GNPs-HRP as detection probe.” Analytical Biochemistry, vol. 534, pp. 56-63, 2017.
[23] 陳彥廷(2009)。《生物醫學的磁奈米粒子研究回顧》 國立台北科科大學生物科技研究所碩士學位論文，未出版，台北市
[24] W. Brullot, N. K. Reddy, J. Wouters, V. K. Valev, B. Goderis, J. Vermant, and T. Verbiest, J. Magn. Magn. Mater. “Versatile ferrofluids based on polyethylene glycol coated iron oxide nanoparticles.” Journal of Magnetism and Magnetic Materials, vol. 324, 1919, Feb 2012.
[25] 陳俊言(2012)。《單頻交流磁化率應用於C-reative Protein之磁減量研究》 國立台灣師範大學光電科技研究所碩士論文，未出版，台北市
[26] Z. Q. Qiu, Y. W. Du, H. Tang, and J. C. Walker, “A Mössbauer study of fine iron particles (invited).” Journal of Applied Physics 63, 4100, 1988.